Our goal is to understand the roles of both bacterial and host factors in the pathogenesis of infections caused by Neisseria meningitidis. This organism is a significant cause of meningitis in many parts of the world, despite available vaccines for some (but not all) meningococcal serogroups. A particular emphasis of this project is on the structure, regulation, and role in pathogenesis of the surface proteins of the meningococcus. The general strategy is to use the techniques and approaches of molecular genetics to study the proteins themselves, and to use the mouse model for meningococcal infection to study the role of the proteins in virulence. The specific aims involve studies on two different outer membrane proteins: the class 5 proteins, and the H.8 antigen. The class 5 proteins provide an example of the variability of the meningococcal surface, while the H.8 antigen is unusual in its ubiquitous presence on all meningococci (and gonococci). The experiments on the class 5 proteins will concentrate on describing the process of class 5 protein variation, and on determining if the ability of the meningococcus to vary its complement of class 5 proteins is important in pathogenesis of experinental meningococcal infection. The studies on the H.8 antigen will focus on understanding more about the structure of the protein and its possible role in virulence. In addition, the ability of H.8-specific antibody to protect the mice against meningococcal infection will be measured. Information from these studies will be important in learning more about the pathogenesis of meningococcal infection, and about the role of specific surface components in that process. In addition, the results of these experiments may be useful in assessing the potential use of specific surface proteins in vaccines for prevention of meningococcal disease.